New hope for kids with rare immune disease: drug targets root cause

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Diagnosis and main criteria for inclusion and exclusion: Patients must satisfy all of the following criteria at the screening visit unless otherwise stated: 1. Patient is male or female and between the age of 4 to 11 years old at the time of the first study procedure. 2. Patient weighs ≥13 kg and \<45 kg at baseline. 3. Patient has a confirmed PI3Kδ genetic mutation of either the PIK3CD (APDS1) or PIK3R1 (APDS2) gene. 4. Patient has at least 1 measurable nodal lesion on magnetic resonance imaging/low-dose computed tomography within 6 months of screening. 5. Patient has nodal or extranodal lymphoproliferation and clinical findings consistent with APDS (eg, a history of repeated oto-sino-pulmonary infections and/or organ dysfunction consistent with APDS). 6. Patient has the ability to ingest unaltered study-related medications without difficulty in the investigator's opinion. 7. At screening, vital signs (systolic blood pressure \[BP\], diastolic BP, and pulse rate) will be assessed in the sitting position after the patient has been at rest for at least 3 minutes. Patient's sitting vital signs should be within the following ranges: * Systolic BP: Less than the 95th percentile adjusted for sex, age, and height percentile. * Diastolic BP: Less than the 95th percentile adjusted for sex, age, and height percentile. * Heart rate (HR): i) Age 4 to \<10 years: 60 to 140 bpm ii) Age ≥10 years: 50 to 100 bpm 8. Institutional review board-/independent ethics committee-approved written informed consent/assent and privacy language as per national and local regulations must be obtained from the patient and parent/legal guardian prior to any study-related procedures. 9. Patient parent/legal guardian is willing and able to complete the informed consent/assent process and comply with study procedures and visit schedule. 10. Patient parent/legal guardian agrees patient will not participate in any other interventional study while enrolled in this study. 11. Female patients should be of non-childbearing potential at screening (should not have reached menarche). Male patients with partners of childbearing potential should be willing to use a highly effective method of contraception for at least 30 days after the last study procedure if at risk of pregnancy. 12. Female patient and parent/legal guardian must agree to the following if menses develops after screening, up to 30 days after the last study procedure: * True sexual abstinence defined as refraining from heterosexual activity during the entire period of the study through 6 months post-study or * Using a highly effective method of contraception for at least 30 days after the last study procedure if at risk of pregnancy. Patients will be excluded from the study if they satisfy any of the following criteria at the screening visit unless otherwise stated: 1. Patient has previous or concurrent use of immunosuppressive medication such as: a. An mTOR inhibitor (eg, sirolimus, rapamycin, everolimus) or a PI3Kδ inhibitor (selective or non-selective PI3K inhibitors) within 6 weeks prior to first dose. i. Short-term use for up to a total of 5 days is allowed but only up to 1 month prior to enrollment in the study. b. B cell depleters (eg, rituximab) within 6 months prior to first dose of study medication. i. If patient has received prior treatment with a B cell depleter, absolute B lymphocyte counts in the blood must have regained normal values. c. Belimumab or cyclophosphamide within 6 months prior to first dose of study medication. d. Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine, or methotrexate within 3 months prior to first dose of study medication. e. Systemic glucocorticoids above a dose equivalent to either ≥2 mg/kg of body weight or ≥20 mg/day of prednisone/prednisolone or equivalent. f. Other immunosuppressive medication where effects are expected to persist at start of dosing of study medication. 2. Patient has a history or current diagnosis of electrocardiogram (ECG) abnormalities indicating significant risk of safety for patients participating in the study such as: 1. History of familial long QT syndrome or known family history of Torsades de Pointes. 2. Concomitant clinically significant cardiac arrhythmias (eg, sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular block without a pacemaker). 3. Resting QTc (Fridericia preferred, but Bazett acceptable) \>460 msec if the measurement is confirmed with an additional ECG repeated as soon as possible. 4. Concomitant use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of the study. 3. Patient is currently using a medication known to be a strong inhibitor or moderate or strong inducer of isoenzyme cytochrome P450 (CYP)3A, if treatment cannot be discontinued or switched to a different medication prior to starting study treatment. 4. Patient is currently using medications that are metabolized by isoenzyme CYP1A2 and have a narrow therapeutic index (drugs whose exposure-response indicates that increases in their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns \[eg, Torsades de Pointes\]). 5. Patient had been administered live vaccines (this includes any attenuated live vaccines) starting from 6 weeks before the anticipated first study drug administration, during the study, and up to 7 days after the last dose of leniolisib. 6. Patient has clinically significant abnormalities in hematology or clinical chemistry (blood chemistry or urinalysis) parameters as determined by the investigator or medical monitor. 7. Patient has liver disease or liver injury as indicated by clinically significant abnormal liver function tests (alanine aminotransferase and aspartate aminotransferase \>2.5 times upper limit of normal), history of renal injury/renal disease (eg, renal trauma, glomerulonephritis, or one kidney only), or presence of impaired renal function as indicated by a serum creatinine level \>1.5 mg/dL (133 μmol/L). 8. Patient has moderate or severe hepatic impairment (Child-Pugh Class B or C). 9. Patient is receiving concurrent treatment with another investigational therapy or use of another investigational therapy less than 4 weeks from the first study procedure. 10. Patient has active hepatitis B (eg, hepatitis B surface antigen reactive) or active hepatitis C (eg, hepatitis C virus RNA \[qualitative\] is detected) at screening. 11. Patient has human immunodeficiency virus (HIV) infection (HIV 1 or 2) at screening. 12. Patient has a positive coronavirus disease 19 result (polymerase chain reaction or antigen) within 1 week prior to first dose. The patient can be rescreened after a subsequent negative result. 13. Patient has a history of malignancy (except lymphoma) within 3 years before the first study procedure or has evidence of residual disease from a previously diagnosed malignancy. 14. Patient has a previous diagnosis of lymphoma that has been treated with chemotherapy, radiotherapy, or transplant within 1 year of the first study procedure or is anticipated to require lymphoma treatment within 6 months of the first study procedure. 15. Patient has a history of uncontrolled diabetes mellitus within 3 months of the first study procedure. 16. Patient has had major surgery requiring hospitalization or radiotherapy within 4 weeks prior to the first study procedure. 17. Patient has uncontrolled chronic or recurrent infectious disease (with the exception of those that are considered to be characteristic of APDS) or evidence of tuberculosis infection as defined by a positive Mantoux tuberculin skin test at screening. If presence of latent tuberculosis is established, then treatment according to local country guidelines must have been completed before patients can be considered for enrollment. 18. Patient has a known allergy or history of hypersensitivity to study defined medications or any ingredients of the medications, including the following common excipients: * Lactose monohydrate * Microcrystalline cellulose * Sodium starch glycolate (Type A) * Hypromellose * Magnesium stearate * Colloidal silicon dioxide * Opadry yellow 19. Patient has a planned or expected major surgical procedure. 20. Patient or parent/legal guardian is unable or unwilling to comply with study procedures or is unable to travel for repeat visits. 21. Patient or parent/legal guardian is unwilling to keep study results/observations confidential or to refrain from posting confidential study results/observations on social media sites. 22. Patient or parent/legal guardian refuses to sign consent/assent form. 23. Patient has other underlying medical condition that, in the opinion of the investigator, would impair the ability of the patient to receive or tolerate the planned procedures or follow-up.